17-47347844-G-T

Variant names:

• chr17-47347844-G-T
• NM_152347.5:c.554G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152347.5(EFCAB13):​c.554G>T​(p.Arg185Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,377,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: EFCAB13 NM_152347.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFCAB13	NM_152347.5	c.554G>T	p.Arg185Leu	missense_variant	Exon 9 of 25	ENST00000331493.7	NP_689560.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFCAB13	ENST00000331493.7	c.554G>T	p.Arg185Leu	missense_variant	Exon 9 of 25	1	NM_152347.5	ENSP00000332111.2
EFCAB13	ENST00000517484.5	c.517+2746G>T		intron_variant	Intron 8 of 21	2		ENSP00000430048.1
EFCAB13	ENST00000517310.5	c.73+2746G>T		intron_variant	Intron 9 of 10	2		ENSP00000466136.1
EFCAB13	ENST00000520776.5	n.651+2746G>T		intron_variant	Intron 6 of 13	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1377690 Hom.: 0 Cov.: 30 AF XY: 0.00000295 AC XY: 2 AN XY: 676892

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000189

Gnomad4 OTH exome AF: 0.0000177

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.32
MutPred		0.44		Gain of helix (P = 0.0117);
MVP		0.17
MPC		0.64
ClinPred		0.68	D
GERP RS		-0.025
Varity_R		0.18
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.62		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.62		Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-45425210; COSMIC: COSV104644447; COSMIC: COSV104644447;